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FEBS Lett. 2010 Apr 16;584(8):1571-6. doi: 10.1016/j.febslet.2010.03.012. Epub 2010 Mar 10.

Alpha-synuclein induced membrane depolarization and loss of phosphorylation capacity of isolated rat brain mitochondria: implications in Parkinson's disease.

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Department of Biochemistry, Institute of Postgraduate Medical Education and Research, Kolkata, India.


This study demonstrates that in vitro incubation of isolated rat brain mitochondria with recombinant human alpha-synuclein leads to dose-dependent loss of mitochondrial transmembrane potential and phosphorylation capacity. However, alpha-synuclein does not seem to have any significant effect on the activities of respiratory chain complexes under similar conditions of incubation suggesting that the former may impair mitochondrial bioenergetics by direct effect on mitochondrial membranes. Moreover, the recombinant wild type alpha-synuclein and different mutant forms (A30P, A53T and E46K) have essentially similar effects on rat brain isolated mitochondria. The results are significant in view of the fact that alpha-synucleinopathy is involved in the pathogenesis of Parkinson's disease.

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